Effect of protein kinase Cbeta inhibition on renal hemodynamic function and urinary biomarkers in humans with type 1 diabetes: a pilot study.
OBJECTIVE
The aim of this study was to examine the effect of protein kinase Cbeta inhibition with ruboxistaurin on renal hemodynamic function and urinary biomarkers (monocyte chemoattractant protein-1 [MCP-1] and epidermal growth factor) in renin angiotensin system blockade-treated type 1 diabetic subjects.


METHODS
Albuminuric subjects were randomized (2:1) to ruboxistaurin (32 mg daily; n = 13) or placebo (n = 7) for 8 weeks. Renal hemodynamic function was measured during clamped euglycemia or hyperglycemia and before and after ruboxistaurin or placebo.


RESULTS
Ruboxistaurin was not associated with between-group differences during clamped euglycemia or hyperglycemia. In a post hoc analysis comparing hyperfilterers with normofilterers during euglycemia, glomerular filtration rate and MCP-1 decreased, whereas the epidermal growth factor-to-MCP-1 ratio increased in hyperfilterers versus normofilterers (all P < 0.05).


CONCLUSIONS
The effect of ruboxistaurin is modest and dependent, at least in part, on the level of ambient glycemia and baseline glomerular filtration rate.
Cherney
David Z I
DZ
Division of Medicine, University Health Network, Toronto, Canada. david.cherney@utoronto.ca
Konvalinka
Ana
A
Zinman
Bernard
B
Diamandis
Eleftherios P
EP
Soosaipillai
Anton
A
Reich
Heather
H
Lorraine
Joanne
J
Lai
Vesta
V
Scholey
James W
JW
Miller
Judith A
JA
D000419:Albuminuria / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000187:drug effects / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000652:urine; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008301:Maleimides / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D004815:Epidermal Growth Factor; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta